tbuckley/cabot-search huggingface dataset:
Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes
Authors: Tara T.M. Lee, Corinne Collett, Simon Bergford, Sara Hartnell, Eleanor M. Scott, Robert S. Lindsay, Katharine F. Hunt, David R. McCance, Katharine Barnard-Kelly, David Rankin, Julia Lawton, Rebecca M. Reynolds, Emma Flanagan, Matthew Hammond, Lee Shepstone, Malgorzata E. Wilinska, Judy Sibayan, Craig Kollman, Roy Beck, Roman Hovorka, Helen R. Murphy
Journal: New England Journal of Medicine (2023)

Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. Download a PDF of the Research Summary. In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Secondary outcomes included the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, −10.2 percentage points; 95% CI, −13.8 to −6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, −0.31 percentage points; 95% CI, −0.50 to −0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.) QUICK TAKE VIDEO SUMMARYAutomated Insulin for Type 1 Diabetes in Pregnancy 01:56
Plasma Tryptophan-Kynurenine Pathway Metabolites and Risk for Progression to End-Stage Kidney Disease in Patients With Type 2 Diabetes
Authors: Jian-Jun Liu, Jianhong Ching, Hai Ning Wee, Sylvia Liu, Resham L. Gurung, Janus Lee, Yiamunaa M., Huili Zheng, Lye Siang Lee, Keven Ang, Yi Ming Shao, Jean-Paul Kovalik, Tavintharan Subramaniam, Chee Fang Sum, Kumar Sharma, Bryan R. Kestenbaum, Su Chi Lim
Journal: Diabetes Care (2023)

OBJECTIVE We sought to study the associations between plasma metabolites in the tryptophan-kynurenine pathway and the risk of progression to end-stage kidney disease (ESKD) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Plasma tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, and xanthurenic acid concentrations were measured in discovery (n = 1,915) and replication (n = 346) cohorts. External validation was performed in Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes (n = 1,312). The primary outcome was a composite of incident ESKD (progression to estimated glomerular filtration rate [eGFR] &amp;lt;15 mL/min/1.73 m2, sustained dialysis, or renal death). The secondary outcome was annual eGFR decline. RESULTS In the discovery cohort, tryptophan was inversely associated with risk for ESKD, and kynurenine-to-tryptophan ratio (KTR) was positively associated with risk for ESKD after adjustment for clinical risk factors, including baseline eGFR and albuminuria (adjusted hazard ratios [HRs] 0.62 [95% CI 0.51, 0.75] and 1.48 [1.20, 1.84] per 1 SD). High levels of kynurenic acid and xanthurenic acid were associated with low risks of ESKD (0.74 [0.60, 0.91] and 0.74 [0.60, 0.91]). Consistently, high levels of tryptophan, kynurenic acid, and xanthurenic acid were independently associated with a slower eGFR decline, while a high KTR was predictive of a faster eGFR decline. Similar outcomes were obtained in the replication cohort. Furthermore, the inverse association between kynurenic acid and risk of ESKD was externally validated in CRIC participants with diabetes (adjusted HR 0.78 [0.65, 0.93]). CONCLUSIONS Accelerated catabolism of tryptophan in the kynurenine pathway may be involved in progressive loss of kidney function. However, shunting the kynurenine pathway toward the kynurenic acid branch may potentially slow renal progression.
The Clinical Utility of Genetic Testing in the Diagnosis and Management of Adults with Chronic Kidney Disease
Authors: Neera K. Dahl, Michelle S. Bloom, Fouad T. Chebib, Dinah Clark, Maggie Westemeyer, Sara Jandeska, Zhiji Zhang, Hila Milo-Rasouly, Victoria Kolupaeva, Maddalena Marasa, Varshasb Broumand, Richard A. Fatica, Dominic S. Raj, Zachary P. Demko, Kyle Marshall, Sumit Punj, Hossein Tabriziani, Sangeeta Bhorade, Ali G. Gharavi
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Accurate diagnosis of a patient's underlying cause of CKD can influence management and ultimately overall health. The single-arm, interventional, prospective Renasight Clinical Application, Review, and Evaluation study assessed the utility of genetic testing with a 385 gene kidney disease panel on the diagnosis and management of 1623 patients with CKD. Among 20.8% of patients who had positive genetic findings, half resulted in a new or reclassified diagnosis. In addition, a change in management because of genetic testing was reported for 90.7% of patients with positive findings, including treatment changes in 32.9%. These findings demonstrate that genetic testing has a significant effect on both CKD diagnosis and management. Background Genetic testing in CKD has recently been shown to have diagnostic utility with many predicted implications for clinical management, but its effect on management has not been prospectively evaluated. Methods Renasight Clinical Application, Review, and Evaluation RenaCARE (ClinicalTrials.gov NCT05846113) is a single-arm, interventional, prospective, multicenter study that evaluated the utility of genetic testing with a broad, 385 gene panel (the Renasight TM test) on the diagnosis and management of adult patients with CKD recruited from 31 US-based community and academic medical centers. Patient medical history and clinical CKD diagnosis were collected at enrollment. Physician responses to questionnaires regarding patient disease categorization and management were collected before genetic testing and 1 month after the return of test results. Changes in CKD diagnosis and management after genetic testing were assessed. Results Of 1623 patients with CKD in 13 predefined clinical disease categories (ages, 18–96; median, 55 years), 20.8% ( n =338) had positive genetic findings spanning 54 genes. Positive genetic findings provided a new diagnosis or reclassified a prior diagnosis in 48.8% of those patients. Physicians reported that genetic results altered the management of 90.7% of patients with a positive genetic finding, including changes in treatment plan, which were reported in 32.9% of these patients. Conclusions Genetic testing with a CKD-focused 385 gene panel substantially refined clinical diagnoses and had widespread implications for clinical management, including appropriate treatment strategies. These data support the utility of broader integration of panels of genetic tests into the clinical care paradigm for patients with CKD. Clinical Trial registry name and registration number ClinicalTrials.gov, NCT05846113.
Technology Use and Glycemic Outcomes during Pregnancy with Type 1 Diabetes
Authors: Satish K. Garg, Sarit Polsky
Journal: New England Journal of Medicine (2023)

Many of us may remember the 1989 movie Steel Magnolias, in which Julia Roberts played the role of someone with type 1 diabetes. As in the movie, at that time women with diabetes were discouraged from becoming pregnant because of poor maternal and fetal outcomes. Fortunately, we have come a long way since then, given the availability of new insulin analogues (long-acting and rapid-acting) and technological advances, including continuous glucose monitoring, insulin pumps, and automated insulin-delivery (also known as closed-loop) systems.1 The Diabetes Control and Complications Trial also showed that intensive insulin therapy and patients' frequent self-monitoring of glucose levels . . .
Complete Absence of FAPI Uptake in a Patient With Aggressive Diffuse Large B-Cell Lymphoma Involving Multiple Nodal and Extranodal Sites
Authors: Li Lu, Ji Bin
Journal: Clinical Nuclear Medicine (2023)

A 73-year-old man with histopathologically confirmed diffuse large B-cell lymphoma underwent both 18 F-FDG and 18 F-FAPI PET/CT. Although 18 F-FDG PET showed abnormally increased tracer uptake in multiple nodal sites and organs, indicating the aggressiveness of the disease status, 18 F-FAPI PET showed no obvious FAPI uptake in any of the FDG-avid lesions. Our case suggests that low expression of FAP in diffuse large B-cell lymphoma, as indicated by FAPI PET, might help determine a subgroup of patients with poorer outcome.
When Can Causal-Analytic Methods Inform Design-Based Research?
Authors: Nima S. Hejazi
Journal: JAMA Network Open (2023)

Matthias Pierce, PhD; Yushi Bai, PhD; Alicia Nevriana, PhD; Christina Dalman, PhD; Holly F. Hope, PhD; Kyriaki Kosidou, PhD; Anna Ohlis, PhD; Susanne Wicks, PhD; Kathryn M. Abel, PhD
Error in Methods and Figure
Journal: JAMA Network Open (2023)

Xiaozhong Wen, MD, PhD; Minseon V. Chung, BS; Kayla A. Liszewski, MPH; Lauren D. Todoro, BS; Eve M. Giancarlo; Wenxin Zhang; Sara K. Berkelhamer, MD; Maciej L. Goniewicz, PharmD, PhD
Bio-clickable, small extracellular vesicles-COCKTAIL therapy for ischemic stroke
Authors: Khan Haroon, Huitong Ruan, Haoran Zheng, Shengju Wu, Ze Liu, Xiaojing Shi, Yaohui Tang, Guo-Yuan Yang, Zhijun Zhang
Journal: Journal of Controlled Release (2023)

Delivering large therapeutic molecules via the blood-brain barrier to treat ischemic stroke remains challenging. NR2B9c is a potent neuroprotective peptide but it's safe and targeted delivery to the brain requires an efficient, natural, and non-immunogenic delivery technique. Small extracellular vesicles (sEVs) have shown great potential as a non-immunogenic, natural cargo delivery system; however, tailoring of its inefficient brain targeting is desired. Here, we coupled rabies virus glycoprotein 29 with sEVs surface via bio-orthogonal click chemistry reactions, followed by loading of NR2B9c, ultimately generating stroke-specific therapeutic COCKTAIL (sEVs-COCKTAIL). Primary neurons and Neuro-2a cells were cultured for in vitro and transient middle cerebral artery occlusion model was used for in vivo studies to evaluate neuron targeting and anti-ischemic stroke potential of the sEVs-COCKTAIL. Bio-clickable sEVs were selectively taken up by neurons but not glial cells. In the in vitro ischemic stroke model of oxygen-glucose deprivation, the sEVs-COCKTAIL exhibited remarkable potential against reactive oxygen species and cellular apoptosis. In vivo studies further demonstrated the brain targeting and increased half-life of bio-clickable sEVs, delivering NR2B9c to the ischemic brain and reducing stroke injury. Treatment with the sEVs-COCKTAIL significantly increased behavioral recovery and reduced neuronal apoptosis after transient middle cerebral artery occlusion. NR2B9c was delivered to neurons binding to post-synaptic density protein-95, inhibiting N-methyl-d-Aspartate receptor-mediated over production of oxidative stress and mitigating protein B-cell lymphoma 2 and P38 proteins expression. Our results provide an efficient and biocompatible approach to a targeted delivery system, which is a promising modality for stroke therapy.
Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial
Authors: Omer Kamer, Ehud Rinott, Gal Tsaban, Alon Kaplan, Anat Yaskolka Meir, Hila Zelicha, Dan Knights, Kieran Tuohy, Francesca Fava, Matthias Uwe Scholz, Oren Ziv, Elad Rubin, Matthias Blüher, Michael Stumvoll, Uta Ceglarek, Karine Clément, Omry Koren, Frank B. Hu, Meir J. Stampfer, Dong D. Wang, Ilan Youngster, Iris Shai
Journal: Gut Microbes (2023)

We previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut microbiome taxa fractions during the weight-loss phase (0-6 m) were differentially associated with weight maintenance following aFMT. Eighty-two abdominally obese/dyslipidemic participants (age = 52 years; 6 m weightloss = -8.3 kg) who provided fecal samples (0 m, 6 m) were included. Frozen 6 m's fecal samples were processed into 1 g, opaque and odorless aFMT capsules. Participants were randomly assigned to receive 100 capsules containing their own fecal microbiota or placebo over 8 m-14 m in ten administrations (adherence rate > 90%). Gut microbiome composition was evaluated using shotgun metagenomic sequencing. Non-core taxa were defined as ≤ 66% prevalence across participants. Overall, 450 species were analyzed. At baseline, 13.3% were classified as core, and Firmicutes presented the highest core proportion by phylum. During 6 m weight-loss phase, abundance of non-core species changed more than core species (P < .0001). Subject-specific changes in core and non-core taxa fractions were strongly correlated (Jaccard Index; r = 0.54; P < .001). Following aFMT treatment, only participants with a low 6 m change in core taxa, and a high change in non-core taxa, avoided 8-14 m weight regain (aFMT = -0.58 ± 2.4 kg, corresponding placebo group = 3.18 ± 3.5 kg; P = .02). In a linear regression model, low core/high non-core 6 m change was the only combination that was significantly associated with attenuated 8-14 m weight regain (P = .038; P = .002 for taxa patterns/treatment intervention interaction). High change in non-core, low-abundance taxa during weight-loss might mediate aFMT treatment success for weight loss maintenance.ClinicalTrials.gov: NCT03020186.
68Ga-PSMA PET/CT in Hepatic Metastasis From Pancreatic Neuroendocrine Tumor
Authors: Shaoming Chen, Zefang Lin, Chao Wang, Weibing Miao
Journal: Clinical Nuclear Medicine (2023)

Abstract A 53-year-old man underwent both 18 F-FDG and 68 Ga-PSMA PET/CT to evaluate a mass in the left upper abdomen. The scans demonstrated intense uptake of both 18 F-FDG and 68 Ga-PSMA in the mass. However, a nodule in the left lobe of the liver showed increased uptake of 68 Ga-PSMA, which was not FDG avid. Histopathological examination after surgical resection of the mass confirmed the diagnosis of pancreatic neuroendocrine tumor (G2). Subsequently, 68 Ga-DOTATATE PET/CT demonstrated intense radioactivity of the nodule in the left lobe of the liver consistent with hepatic metastasis from neuroendocrine tumor.
Potent gene delivery from fluorinated poly(β-amino ester) in adhesive and suspension difficult-to-transfect cells for apoptosis and ferroptosis
Authors: Yihui Deng, Jing Zhang, Ximeng Sun, Liangtao Li, Mandi Zhou, Shuang Liu, Fuying Chen, Chaolan Pan, Ziyi Yu, Ming Li, Wenbin Zhong, Ming Zeng
Journal: Journal of Controlled Release (2023)
Causal effect of elevated body mass index on hidradenitis suppurativa: a two-sample Mendelian randomization study
Authors: Yuanyuan Xu, Linghong Guo, Shuwei Wu, Ting Zhang, Xian Jiang
Journal: British Journal of Dermatology (2023)

A well-known relationship between elevated BMI and hidradenitis suppurativa (HS) has been observed, although the causality or directionality of this association remains unclarified owing to the retrospective nature of studies and common diagnostic delays. Through a Mendelian randomization (MR) analysis, the causal relationship between increased BMI and HS was demonstrated by inverse variance weighted (IVW), weighted median and weighted mode methods. According to the IVW method, the odds ratio for HS was 2.62 for each 1 SD increase in genetically predicted BMI levels. The robustness of this analysis was further confirmed by Cochran’s Q test, MR Egger Intercept test, MR PRESSO global test and ‘leave-one-SNP-out’ analysis.
Pangolin Genomes Offer Key Insights and Resources for the World’s Most Trafficked Wild Mammals
Authors: Sean P Heighton, Rémi Allio, Jérôme Murienne, Jordi Salmona, Hao Meng, Céline Scornavacca, Armanda D S Bastos, Flobert Njiokou, Darren W Pietersen, Marie-Ka Tilak, Shu-Jin Luo, Frédéric Delsuc, Philippe Gaubert
Journal: Molecular Biology and Evolution (2023)

Abstract Pangolins form a group of scaly mammals that are trafficked at record numbers for their meat and purported medicinal properties. Despite their conservation concern, knowledge of their evolution is limited by a paucity of genomic data. We aim to produce exhaustive genomic resources that include 3,238 orthologous genes and whole-genome polymorphisms to assess the evolution of all eight extant pangolin species. Robust orthologous gene-based phylogenies recovered the monophyly of the three genera and highlighted the existence of an undescribed species closely related to Southeast Asian pangolins. Signatures of middle Miocene admixture between an extinct, possibly European, lineage and the ancestor of Southeast Asian pangolins, provide new insights into the early evolutionary history of the group. Demographic trajectories and genome-wide heterozygosity estimates revealed contrasts between continental versus island populations and species lineages, suggesting that conservation planning should consider intraspecific patterns. With the expected loss of genomic diversity from recent, extensive trafficking not yet realized in pangolins, we recommend that populations be genetically surveyed to anticipate any deleterious impact of the illegal trade. Finally, we produce a complete set of genomic resources that will be integral for future conservation management and forensic endeavors for pangolins, including tracing their illegal trade. These comprise the completion of whole-genomes for pangolins through the hybrid assembly of the first reference genome for the giant pangolin (Smutsia gigantea) and new draft genomes (∼43x–77x) for four additional species, as well as a database of orthologous genes with over 3.4 million polymorphic sites.
Generative Artificial Intelligence for Chest Radiograph Interpretation in the Emergency Department
Authors: Jonathan Huang, Luke Neill, Matthew Wittbrodt, David Melnick, Matthew Klug, Michael Thompson, John Bailitz, Timothy Loftus, Sanjeev Malik, Amit Phull, Victoria Weston, J. Alex Heller, Mozziyar Etemadi
Journal: JAMA Network Open (2023)

Multimodal generative artificial intelligence (AI) methodologies have the potential to optimize emergency department care by producing draft radiology reports from input images.To evaluate the accuracy and quality of AI-generated chest radiograph interpretations in the emergency department setting.This was a retrospective diagnostic study of 500 randomly sampled emergency department encounters at a tertiary care institution including chest radiographs interpreted by both a teleradiology service and on-site attending radiologist from January 2022 to January 2023. An AI interpretation was generated for each radiograph. The 3 radiograph interpretations were each rated in duplicate by 6 emergency department physicians using a 5-point Likert scale.The primary outcome was any difference in Likert scores between radiologist, AI, and teleradiology reports, using a cumulative link mixed model. Secondary analyses compared the probability of each report type containing no clinically significant discrepancy with further stratification by finding presence, using a logistic mixed-effects model. Physician comments on discrepancies were recorded.A total of 500 ED studies were included from 500 unique patients with a mean (SD) age of 53.3 (21.6) years; 282 patients (56.4%) were female. There was a significant association of report type with ratings, with post hoc tests revealing significantly greater scores for AI (mean [SE] score, 3.22 [0.34]; P < .001) and radiologist (mean [SE] score, 3.34 [0.34]; P < .001) reports compared with teleradiology (mean [SE] score, 2.74 [0.34]) reports. AI and radiologist reports were not significantly different. On secondary analysis, there was no difference in the probability of no clinically significant discrepancy between the 3 report types. Further stratification of reports by presence of cardiomegaly, pulmonary edema, pleural effusion, infiltrate, pneumothorax, and support devices also yielded no difference in the probability of containing no clinically significant discrepancy between the report types.In a representative sample of emergency department chest radiographs, results suggest that the generative AI model produced reports of similar clinical accuracy and textual quality to radiologist reports while providing higher textual quality than teleradiologist reports. Implementation of the model in the clinical workflow could enable timely alerts to life-threatening pathology while aiding imaging interpretation and documentation.